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January 2011 Archives : Doctor Durie

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Normally we talk about the "chemistry of life" and we are quite familiar with the development of new chemicals to treat cancers including myeloma. About two years ago, the IMF entering into a research agreement with Prof. Luc Montagnier in Paris, France, the Nobel Laureate, (who discovered the AIDS virus.) We agreed to investigate nucleotide sequences in the blood of patients with MGUS, smoldering myeloma and active myeloma to assess the presence or absence of DNA sequences including virus and/or bacterial related sequences, hints of which we have detected in prior studies.  A number of genetic fragments have been identified using whole gene sequencing techniques.  Using samples obtained in collaboration with Dr. Shaji Kumar and colleagues at the Mayo Clinic in Rochester, Minnesota, the research is moving forward rapidly. 

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However, a new facet has emerged:  Professor Montagnier is convinced that crucial differences can be detected at the electromagnetic level in addition to methods using conventional sequencing and "chemical" testing which are central to the overall project.   In an interview with the Science magazine (science mag.org) December 24, 2010 (330: p 1732 2010) Prof. Montagnier revealed that he will be the leader of a new research institute at the prestigious Jiaotong University in Shanghai, China.1  The main focus will be to investigate "electromagnetic waves produced by DNA in water" or what has been called "water memory," as reported by French immunologist Jacques Benveniste in the journal Nature in 1988.  This topic has been the subject of great controversy, especially in France, but the Chinese are open to, and apparently very keen to fund further research.  Abnormal signals have been found coming from "bacterial DNA in the plasma of many patients" with a range of chronic diseases and cancer.

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As I pondered this interesting new initiative, I opened the morning newspaper to read that an elite group of geophysicists (including NASA scientists) had just detected the release of anti-matter into extraterrestrial space from the upper surfaces of clouds during electrical storms.2  (Yes, anti-matter: think Angles and Demons and the plot to blow up the Vatican.)  Electrons move one way and positrons another: a phenomenon called pair production (particle-antiparticle pairs), which is a relativistic or quantum process.3 

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What could this possibly mean? I had visions of the thunderstorms on Earth millennia ago when many have proposed life emerged.  I recalled the famous book by Edwin Schrodinger (Schrodinger's cat fame):  What is Life? in which he discussed the physical basis of life systems at the level of elementary particles.4  A group of German researchers recently published a book with the same title, which updates these same concepts; that the capture, storage and use of energy and information are key.5  Electromagnetic communication is what brings and keeps everything together and running.  Cooperation between cells or bacteria has been the basis for several recent studies including the direct exchange of electrons between bacteria.6-8  Mae-Wan Ho in The Rainbow and the Worm: The Physics of Organisms explores the quantum nature of life processes.9 She answers the question of "What is life?".  "Life is all the colors of a rainbow in a worm".  Elisabeth Rieper and colleagues at the Center for Quantum Technologies in Singapore recently concluded that quantum entanglement plays a crucial role in explaining the stability and data storage of the DNA double helix.10

I was absolutely certain that I was uncertain what all this means!

But, it seems that understanding life at the sub-molecular and electromagnetic level is now possible.  Uncertainty is the fundamental basis for a new research project.  So, I wish Prof. Montagnier "fair winds and following seas" as he heads into new areas of water research. This could be a new French revolution of ideas.  But will it be Viva la France or la Chine?  I see a new iPad APP in my future:  "The Electromagnetic techniques for myeloma diagnosis and treatment."          

References

  1. Enserink M. French Nobelist escapes 'intellectual terror' to pursue radical ideas in China. Science. 330:1732; 2010.
  2. Maugh TH. What's in a thunderstorm? Antimatter for one. LA Times, January 11, 2011.
  3. Briggs MS, Connaughton V, Wilson-Hodge C, et al. Electron-positron beams from terrestrial lightening observed with Fermi GBM. Geophysical Research Letters. Pre-published online. 2011.
  4.  Schrodinger E, What is Life?. Cambridge University Press; London & New York, 1955.
  5. Durr HP, Popp FA, Schommers W.  What is life? Scientific approaches and philosophical positions. World Scientific; New Jersey, 2002.
  6. Summers ZM, Fogarty HE, Leang C, et al. Direct exchange of electrons within aggregates of an evolved syntrophic coculture of anaerobic bacteria. Science. 330:1413-1415; 2010.
  7.  Kozlowski L. Discovering how microbes cooperate. LA Times, Jan 1, 2011.
  8. Smith J, Van Dyken JD, Zee PC. A generalization of Hamilton's rule for the evolution of microbial cooperation. Science. 328:1700-1705; 2010.
  9. Ho M-W. The Rainbow and the Worm- The Physics of Organisms. World Scientific; New Jersey, 2006.
  10. Rieper E, Anders J, Vedral V. The relevance of continuous variable entanglement in DNA. arXiv:1006.4053v1 [quant-ph].

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It is important to remember that new drugs are new.  In May 2010 Glaxo (GSK) suspended a study with SRT501, Sirtris' formulation of Resveratrol, the minor ingredient in red wine linked to longevity and possible anti-myeloma activity.  Now, in December 2010, Fierce Biotech posted that Sirtris (bought by Glaxo for $720 million in 2008) had abandoned SRT501 altogether because of lack of efficacy, and in the case of the myeloma trial, life threatening kidney toxicity.  One criticism of the halted myeloma trial was that over ten times the active dose of resveratrol was used and most likely accounted for the kidney toxicity.

Resveratrol is a natural product found in grapes and present in red wine.  This natural product is available over the counter, for example, in the Biotivia Transmax product (500mg capsules).  The question is whether this natural compound, which extended the life of obese mice in Prof. David Sinclair's original studies, or whether patentable drugs activating just the SIRT I pathway should be the focus for research.1-5  The new synthetic small molecules target the SIRT I pathway whereas the original resveratrol hits many targets which may account for its benefit.  And what should the dose be?

hedgehog.jpgAssessing anti-aging and possible anti-myeloma effects takes time and patience which is an increasingly rare commodity in the highly charged culture of drug development.  The human body is a delicate machine.  Giving more of a drug is not necessarily better: maybe there is an ideal lower dose given over time.  This was recently illustrated with the impact of a baby aspirin in reducing the occurrence of heart disease and cancer after at least 5 years of use.6-8

Another example is hedgehog inhibitors. 9 Matsui and colleagues10 showed that a critical pathway in the activation of the myeloma stem cell is the Hh (Hedgehog) pathway.  Blocking this could prevent myeloma "reseeding" in the bone marrow after successful treatment, and possiblly lead to a cure.  A chemical was immediately available capable of blocking the hedgehog gene and called cyclopamine named after the birth defect (of a single eye) in sheep grazing on wild corn lily containing the agent.  Again the same story emerged: drug companies tried to replicate the effects of cyclopamine (which has some potentially dangerous side effects) with synthetic compounds.   In this case, simply blocking this one pathway turned out to be not that effective in myeloma.  But wait, at the recent ASH meeting in Florida another researcher, Dr. Guido Tricot, showed that blocking 2 pathways, Hh plus Wnt, showed remarkable benefit in the laboratory.  Tricot tested a combination of cyclopamine plus itraconazole to block Hh and another compound CY10404 (cox-2 inhibitor similar to Celebrex®) to block the additional Wnt pathway.  Perhaps persistence and patience can pay off in coming up with an effective strategy.

So new ideas are new.  It takes time to figure out the best way forward.  This is frustrating, but necessary.  The very good news is that these are exciting new ideas and progress is being made.  Stay Tuned.

References

  1. Wade N. Doubt on Anti-Aging Molecule as Drug Trial Stops, The New York Times; January 11, 2011.
  2. Saunders LR, Verdin E. Stress response and aging. Science; 323:1021-1022; 2009.
  3. Brooks CL, Gu W. How does SIRT 1 affect metabolism, senescence and cancer?. Cancer; 9:123-128; 2009.
  4. Saunders LR, Verdin E. Sirtuins: critical regulators at the crossroads between cancer and aging. Oncogene; 26:5489-5504; 2007.
  5. Baur JA, Sinclair DA. Therapeutic potential of resveratrol: the in vivo evidence. Nature Reviews; 5:493-506; 2006.
  6. Jacobs EJ. Will an aspirin a day help keep fatal cancer away?. The Lancet; 377:3-4; 2011.
  7. Rothwell PM, Fowkes FGR, Belch JFF, et al. Effect of daily apsirin on long-term risk of death due to cancer: analysis of individual patient data from randomized trials. The Lancet; 377:31-41; 2011.
  8. Rothwell PM, Wilson M, Elwin C-E, et al. Long-term effect of aspirin on colorectal cancer incidence and mortality: 20-year follow-up of five randomized trials. The Lancet; 376:1741-1750; 2010.
  9. Low JA, de Sauvage FJ. Clinical experience with hedgehog pathway inhibitors. Journal of Clinical Oncology; 28(36):5321-5326; 2010.
  10. Matsui, et. al., ASH 2010 "Origin Of The Myeloma Stem Cell", IMF Webcast, http://tinyurl.com/matsuistemcell

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